\ BIP! Finder for COVID-19 - Impact-based ranking

BIP! Finder for COVID-19

This version of BIP! Finder aims to ease the exploration of COVID-19-related literature by enabling ranking articles based on various impact metrics.

Last Update: 18 - 01 - 2023 (628506 entries)

Provided impact measures:
Popularity: Citation-based measure reflecting the current impact.
Influence: Citation-based measure reflecting the total impact.
Reader Attention: The current number of Mendeley readers.
Social Media Attention: The number of recent tweets related to this article.
*More details on these impact measures can be found here.
Score interpretations:
Exceptional score (in top 0.01%).
Substantial score (in top 1%).
Average score (in bottom 99%).
Score not available.
Main data sources:
CORD-19 dataset(1) (list of papers)
LitCovid hub(2) (list of papers)
PMC & PubMed (citations)
Mendeley (number of readers)
COVID-19-TweetIDs(3) (tweets)

Use:  Impact  Relevance & Impact
TitleVenueYearImpactSource
8351Development of a quantitative segmentation model to assess the effect of comorbidity on patients with COVID-19  

BACKGROUND: The coronavirus disease 2019 (COVID-19) has brought a global disaster. Quantitative lesions may provide the radiological evidence of the severity of pneumonia and further to assess the effect of comorbidity on patients with COVID-19. METHODS: 294 patients with COVID-19 were enrolled from February, 24, 2020 to June, 1, 2020 from six centers. Multi-task Unet network was used to segment the whole lung and lesions from chest CT images. This deep learning method was pre-trained in 650 CT images (550 in primary dataset and 100 in test dataset) with COVID-19 or community-acquired pneumonia and Dice coefficients in test dataset were calculated. 50 CT scans of 50 patients (15 with comorbidity and 35 without comorbidity) were random selected to mark lesions manually. The results will be compared with the automatic segmentation model. Eight quantitative parameters were calculated based on the segmentation results to evaluate the effect of comorbidity on patients with COVID-19. RESULTS: Quantitative segmentation model was proved to be effective and accurate with all Dice coefficients more than 0.85 and all accuracies more than 0.95. Of the 294 patients, 52 (17.7%) patients were reported having at least one comorbidity; 14 (4.8%) having more than one comorbidity. Patients with any comorbidity were older (P < 0.001), had longer incubation period (P < 0.001), were more likely to have abnormal laboratory findings (P < 0.05), and be in severity status (P < 0.001). More lesions (including larger volume of lesion, consolidation, and ground-glass opacity) were shown in patients with any comorbidity than patients without comorbidity (all P < 0.001). More lesions were found on CT images in patients with more comorbidities. The median volumes of lesion, consolidation, and ground-glass opacity in diabetes mellitus group were largest among the groups with single comorbidity that had the incidence rate of top three. CONCLUSIONS: Multi-task Unet network can make quantitative CT analysis of lesions to assess the effect of comorbidity on patients with COVID-19, further to provide the radiological evidence of the severity of pneumonia. More lesions (including GGO and consolidation) were found in CT images of cases with comorbidity. The more comorbidities patients have, the more lesions CT images show.

Eur J Med Res2020       LitCov and CORD-19
8352Diminishing Immune Responses against Variants of Concern in Dialysis Patients 4 Months after SARS-CoV-2 mRNA Vaccination  

Patients undergoing chronic hemodialysis were among the first to receive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations because of their increased risk for severe coronavirus disease and high case-fatality rates. By using a previously reported cohort from Germany of at-risk hemodialysis patients and healthy donors, where antibody responses were examined 3 weeks after the second vaccination, we assessed systemic cellular and humoral immune responses in serum and saliva 4 months after vaccination with the Pfizer-BioNTech BNT162b2 vaccine using an interferon-γ release assay and multiplex-based IgG measurements. We further compared neutralization capacity of vaccination-induced IgG against 4 SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Delta) by angiotensin-converting enzyme 2 receptor-binding domain competition assay. Sixteen weeks after second vaccination, compared with 3 weeks after, cellular and humoral responses against the original SARS-CoV-2 isolate and variants of concern were substantially reduced. Some dialysis patients even had no detectable B- or T-cell responses.

Emerg Infect Dis2022       LitCov and CORD-19
8353China's global engagement to fight the novel coronavirus pandemic  

The world is confronted by the current pandemic of coronavirus disease 2019 (COVID-19), which is a common threat to the whole of humanity. In the process of fighting COVID-19 domestically, China had attached great importance to international cooperation, such as the sharing of information on the pandemic with the international community, providing bilateral and multilateral assistance to other affected countries, etc. However, due to the severity of this pandemic, global solidarity is necessary to conquer it, and to improve global public health governance.

Glob Health Res Policy2020       LitCov and CORD-19
8354COVID-19 Associated Mucormycosis: An Opportunistic Fungal Infection. A Case Series and Review  

Background : A surge in COVID-19 associated mucormycosis cases has been observed during the second COVID-19 wave, in summer 2021. The majority of cases were reported from India. The Delta variant (B.1.617.2) was the most common variant circulating at that time. Mucormycosis is an angio-invasive fungal opportunistic infection with high morbidity and mortality. Case presentation : We present 10 cases of COVID-19 associated Rhino-orbital and rhino-orbital-cerebral mucormycosis managed in a secondary hospital in Oman. The median time for developing mucormycosis was two weeks from the COVID-19 diagnosis. All patients were known or newly diagnosed with to have poorly controlled diabetes mellitus. Five patients received corticosteroid therapy for COVID-19. Three patients had severe COVID-19 infection and died due to severe ARDS and septic shock. Another three patients died with advanced mucormycosis and cerebral involvement. Despite aggressive medical and surgical intervention, the mortality rate was 60% (6/10). Conclusion : Mucormycosis is an aggressive opportunistic infection with high morbidity and mortality that requires prompt recognition and urgent intervention. Uncontrolled blood sugar, the use of corticosteroids and immune dysfunction due to COVID-19 patients and uncontrolled blood sugar, all are important risk factors for development of mucormycosis. Worse outcomes are associated with poor glycemic control despite aggressive medical and surgical interventions.

Int J Infect Dis2022       LitCov and CORD-19
8355Evidence of airborne transmission of the severe acute respiratory syndrome virus  

N/A

N Engl J Med2004       CORD-19
8356Timing of State and Territorial COVID-19 Stay-at-Home Orders and Changes in Population Movement-United States, March 1-May 31, 2020  

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is thought to spread from person to person primarily by the respiratory route and mainly through close contact (1). Community mitigation strategies can lower the risk for disease transmission by limiting or preventing person-to-person interactions (2). U.S. states and territories began implementing various community mitigation policies in March 2020. One widely implemented strategy was the issuance of orders requiring persons to stay home, resulting in decreased population movement in some jurisdictions (3). Each state or territory has authority to enact its own laws and policies to protect the public's health, and jurisdictions varied widely in the type and timing of orders issued related to stay-at-home requirements. To identify the broader impact of these stay-at-home orders, using publicly accessible, anonymized location data from mobile devices, CDC and the Georgia Tech Research Institute analyzed changes in population movement relative to stay-at-home orders issued during March 1-May 31, 2020, by all 50 states, the District of Columbia, and five U.S. territories.* During this period, 42 states and territories issued mandatory stay-at-home orders. When counties subject to mandatory state- and territory-issued stay-at-home orders were stratified along rural-urban categories, movement decreased significantly relative to the preorder baseline in all strata. Mandatory stay-at-home orders can help reduce activities associated with the spread of COVID-19, including population movement and close person-to-person contact outside the household.

MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
8357Exploring the impact of media and information on self-reported intentions to vaccinate against COVID-19: A qualitative interview-based study  

N/A

Hum Vaccin Immunother2022       LitCov and CORD-19
8358Prevalence of SARS-CoV-2 antibodies in pediatric healthcare workers  

OBJECTIVES: To determine SARS-CoV-2-antibody prevalence in pediatric healthcare workers (pHCWs). DESIGN: Baseline prevalence of anti-SARS-CoV-2-IgG was assessed in a prospective cohort study from a large pediatric healthcare facility. Prior SARS-CoV-2 testing history, potential risk factors and anxiety level about COVID-19 were determined. Prevalence difference between emergency department (ED)-based and non-ED-pHCWs was modeled controlling for those covariates. Chi-square test-for-trend was used to examine prevalence by month of enrollment. RESULTS: Most of 642 pHCWs enrolled were 31-40years, female and had no comorbidities. Half had children in their home, 49% had traveled, 42% reported an illness since January, 31% had a known COVID-19 exposure, and 8% had SARS-CoV-2 PCR testing. High COVID-19 pandemic anxiety was reported by 71%. Anti-SARS-CoV-2-IgG prevalence was 4.1%; 8.4% among ED versus 2.0% among non-ED pHCWs (p < 0.001). ED-work location and known COVID-19 exposure were independent risk factors. 31% of antibody-positive pHCWs reported no symptoms. Prevalence significantly (p < 0.001) increased from 3.0% in April-June to 12.7% in July-August. CONCLUSIONS: Anti-SARS-CoV-2-IgG prevalence was low in pHCWs but increased rapidly over time. Both working in the ED and exposure to a COVID-19-positive contact were associated with antibody-seropositivity. Ongoing universal PPE utilization is essential. These data may guide vaccination policies to protect front-line workers.

Int J Infect Dis2021       LitCov and CORD-19
8359'Do I, don't I?' A qualitative study addressing parental perceptions about seeking healthcare during the COVID-19 pandemic  

BACKGROUND: Paediatric emergency departments have seen reduced attendance during the COVID-19 pandemic. Late paediatric presentations may lead to severe illness and even death. Maintaining provision of healthcare through a pandemic is essential. This qualitative study aims to identify changing care-seeking behaviours in child health during the pandemic and ascertain parental views around barriers to care. METHODS: Semistructured interviews were conducted with caregivers of children accessing acute paediatric services in a hospital in North-West London. Thematic content analysis was used to derive themes from the data, using a deductive approach. RESULTS: From interviews with 15 caregivers an understanding was gained of care-seeking behaviours during the pandemic. Themes identified were; influencers of decision to seek care, experience of primary care, other perceived barriers, experiences of secondary care, advice to others following lived experience. Where delays in decision to seek care occurred this was influenced predominantly by fear, driven by community perception and experience and media portrayal. Delays in reaching care were focused on access to primary care and availability of services. Caregivers were happy with the quality of care received in secondary care and would advise friends to seek care without hesitation, not to allow fear to delay them. CONCLUSION: A pandemic involving a novel virus is always a challenging prospect in terms of organisation of healthcare provision. This study has highlighted parental perspectives around access to care and care-seeking behaviours which can inform us how to better improve service functioning during such a pandemic and beyond into the recovery period.

Arch Dis Child2021       LitCov and CORD-19
8360A National US Survey of Pediatric Emergency Department Coronavirus Pandemic Preparedness  

OBJECTIVE: We aim to describe the current coronavirus disease 2019 (COVID-19) preparedness efforts among a diverse set of pediatric emergency departments (PEDs) within the United States. METHODS: We conducted a prospective multicenter survey of PED medical director(s) from selected children’s hospitals recruited through a long established national research network. The questionnaire was developed by physicians with expertise in pediatric emergency medicine, disaster readiness, human factors, and survey development. Thirty-five children’s hospitals were identified for recruitment through an established national research network. RESULTS: We report on survey responses from 25 (71%) of 35 PEDs, of which 64% were located within academic children's hospitals. All PEDs witnessed decreases in non–COVID-19 patients, 60% had COVID-19–dedicated units, and 32% changed their unit pediatric patient age to include adult patients. All PEDs implemented changes to their staffing model, with the most common change impacting their physician staffing (80%) and triaging model (76%). All PEDs conducted training for appropriate donning and doffing of personal protective equipment (PPE), and 62% reported shortages in PPE. The majority implemented changes in the airway management protocols (84%) and cardiac arrest management in COVID patients (76%). The most common training modalities were video/teleconference (84%) and simulation-based training (72%). The most common learning objectives were team dynamics (60%), and PPE and individual procedural skills (56%). CONCLUSIONS: This national survey provides insight into PED preparedness efforts, training innovations, and practice changes implemented during the start of COVID-19 pandemic. Pediatric emergency departments implemented broad strategies including modifications to staffing, workflow, and clinical practice while using video/teleconference and simulation as preferred training modalities. Further research is needed to advance the level of preparedness and support deep learning about which preparedness actions were effective for future pandemics.

Pediatr Emerg Care2020       LitCov and CORD-19
8361Effectiveness of non-pharmaceutical interventions on COVID-19 transmission in 190 countries from 23 January to 13 April 2020  

BACKGROUND: To evaluate and compare the effectiveness of four types of non-pharmaceutical interventions (NPIs) in containing the time-varying effective reproduction number (Rt) of COVID-19. METHODS: This study included 1,908,197 confirmed COVID-19 cases from 190 countries between 23 January and 13 April 2020. The implemented NPIs were categorized into four types: mandatory face mask in public, isolation or quarantine, social distancing and traffic restriction (referred to as mandatory mask, quarantine, distancing, and traffic hereafter, respectively). RESULTS: The implementations of mandatory mask, quarantine, distancing and traffic were associated with changes (95%confidence interval, CI) of -15.14% (-21.79% to -7.93%), -11.40% (-13.66% to -9.07%), -42.94% (-44.24% to -41.60%) and -9.26% (-11.46% to -7.01%) in the Rt of COVID-19 compared with those without the implementation of the corresponding measures. Distancing and the simultaneous implementation of two or more types of NPIs seemed to be associated with a greater decrease in the Rt of COVID-19. CONCLUSION: Our study indicates that NPIs can significantly contain the COVID-19 pandemic. Distancing and the simultaneous implementation of two or more NPIs should be the strategic priorities for containing COVID-19.

Int J Infect Dis2020       LitCov and CORD-19
8362Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome  

[Image: see text] We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID-19 patients and the possible biochemical sequelae of “Post-Acute COVID-19 Syndrome”, colloquially known as long-COVID. Blood samples were taken from patients ca. 3 months after acute COVID-19 infection with further assessment of symptoms at 6 months. Some 57% of the patients had one or more persistent symptoms including respiratory-related symptoms like cough, dyspnea, and rhinorrhea or other nonrespiratory symptoms including chronic fatigue, anosmia, myalgia, or joint pain. Plasma samples were quantitatively analyzed for lipoproteins, glycoproteins, amino acids, biogenic amines, and tryptophan pathway intermediates using Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Metabolic data for the follow-up patients (n = 27) were compared with controls (n = 41) and hospitalized severe acute respiratory syndrome SARS-CoV-2 positive patients (n = 18, with multiple time-points). Univariate and multivariate statistics revealed variable patterns of functional recovery with many patients exhibiting residual COVID-19 biomarker signatures. Several parameters were persistently perturbed, e.g., elevated taurine (p = 3.6 × 10(–3) versus controls) and reduced glutamine/glutamate ratio (p = 6.95 × 10(–8) versus controls), indicative of possible liver and muscle damage and a high energy demand linked to more generalized tissue repair or immune function. Some parameters showed near-complete normalization, e.g., the plasma apolipoprotein B100/A1 ratio was similar to that of healthy controls but significantly lower (p = 4.2 × 10(–3)) than post-acute COVID-19 patients, reflecting partial reversion of the metabolic phenotype (phenoreversion) toward the healthy metabolic state. Plasma neopterin was normalized in all follow-up patients, indicative of a reduction in the adaptive immune activity that has been previously detected in active SARS-CoV-2 infection. Other systemic inflammatory biomarkers such as GlycA and the kynurenine/tryptophan ratio remained elevated in some, but not all, patients. Correlation analysis, principal component analysis (PCA), and orthogonal-partial least-squares discriminant analysis (O-PLS-DA) showed that the follow-up patients were, as a group, metabolically distinct from controls and partially comapped with the acute-phase patients. Significant systematic metabolic differences between asymptomatic and symptomatic follow-up patients were also observed for multiple metabolites. The overall metabolic variance of the symptomatic patients was significantly greater than that of nonsymptomatic patients for multiple parameters (χ(2)p = 0.014). Thus, asymptomatic follow-up patients including those with post-acute COVID-19 Syndrome displayed a spectrum of multiple persistent biochemical pathophysiology, suggesting that the metabolic phenotyping approach may be deployed for multisystem functional assessment of individual post-acute COVID-19 patients.

J Proteome Res2021       LitCov and CORD-19
8363Spring 2020 COVID-19 Surge: Prospective Relations between Demographic Factors, Personality Traits, Social Cognitions and Guideline Adherence, Mask Wearing and Symptoms in a US Sample  

BACKGROUND: To date, much of the research on individual difference correlates of coronavirus guideline adherence is cross-sectional, leaving prospective associations between these factors unaddressed. Additionally, investigations of prospective predictors of mask-wearing, COVID-19 symptoms, and viral testing remain wanting. PURPOSE: The present study examined prospective relations between demographic factors, personality traits, social cognitions and guideline adherence, mask-wearing, symptoms, and viral testing in a U.S. sample (N = 500) during the initial surge of COVID-19 deaths in the United State between late March and early May 2020. METHODS: Guided by a disposition-belief-motivation framework, correlational analyses, and path models tested associations among baseline personality traits, guideline adherence social cognitions, health beliefs, guideline adherence and follow-up guideline adherence, mask-wearing, symptom counts, and 30-day viral testing. RESULTS: Modeling results showed greater baseline agreeableness, conscientiousness, and extraversion were associated with more frequent baseline guideline adherence. More liberal political beliefs, greater guideline adherence intentions, and more frequent guideline adherence at baseline predicted more frequent mask-wearing at follow-up. Sex (female), lower perceived health, and greater neuroticism at baseline predicted greater symptom counts at follow-up. Reports of viral testing were quite low (1.80%), yet were consistent with concurrent national reporting and limited availability of testing. CONCLUSIONS: Results show how inconsistencies and politicization of health policy communication were concomitant with the effects of individual-level political beliefs on mask-wearing during the initial surge. The results further clarify how personality traits related to social responsibility (i.e., agreeableness, conscientiousness) are associated with following new norms for prescribed behaviors and how symptom reporting can be as much a marker of perceived health as emotional stability.

Ann Behav Med2021       LitCov and CORD-19
8364Evaluation of a chemiluminescent enzyme immunoassay-based high-throughput SARS-CoV-2 antigen assay for the diagnosis of COVID-19: The VITROS SARS-CoV-2 Antigen Test  

A high‐throughput, fully automated antigen detection test for SARS‐CoV‐2 is a viable alternative to reverse‐transcription polymerase chain reaction (RT‐qPCR) for mass screening during outbreaks. In this study, we compared RT‐qPCR for viral load and the VITROS® SARS‐CoV‐2 Antigen Test with reference to the results of the LUMIPULSE® SARS‐CoV‐2 Ag Test. Of 128 nasopharyngeal swab specimens taken from patients suspected of being infected with SARS‐CoV‐2, 49 were positive and 79 were negative according to RT‐qPCR. Consistent dose‐dependent detection with VITROS® assay was successfully achieved when using nasopharyngeal swab specimens with Ct values of 32.0 or lesser, whereas the CLEIA‐based LUMIPULSE® assay was able to detect lower viral loads compared with the VITROS® assay. Our results show that the performance of the VITROS® assay was satisfactory for the diagnosis of contagious COVID‐19 patients in the clinical setting. Highlights The performance of the VITROS® SARS‐CoV‐2 Antigen Test was sufficient for the diagnosis of contagious COVID‐19. This test showed high sensitivity and specificity in the detection of SARS‐CoV‐2 in samples with a Ct value of 32 or less.

J Med Virol2021       LitCov and CORD-19
8365Model-based assessment of SARS-CoV-2 Delta variant transmission dynamics within partially vaccinated K-12 school populations  

BACKGROUND: We examined school reopening policies amidst rising transmission of the highly transmissible Delta variant, accounting for vaccination among individuals aged 12 years and older, with the goal of characterizing risk to students and teachers under various within-school non-pharmaceutical interventions (NPIs) combined with specific vaccination coverage levels. METHODS: We developed an individual-based transmission model to simulate transmission of the Delta variant of SARS-CoV-2 among a synthetic population, representative of Bay Area cities. We parameterized the model using community contact rates from vaccinated households ascertained from a household survey of Bay Area families with children conducted between February – April, 2021. INTERVENTIONS AND OUTCOMES: We evaluated the additional infections in students and teachers/staff resulting over a 128-day semester from in-school instruction compared to remote instruction when various NPIs (mask use, cohorts, and weekly testing of students/teachers) were implemented in schools, across various community-wide vaccination coverages (50%, 60%, 70%), and student (≥12 years) and teacher/staff vaccination coverages (50% – 95%). We quantified the added benefit of universal masking over masking among unvaccinated students and teachers, across varying levels of vaccine effectiveness (45%, 65%, 85%), and compared results between Delta and Alpha variant circulation. RESULTS: The Delta variant sharply increases the risk of within-school COVID-transmission when compared to the Alpha variant. In our highest risk scenario (50% community and within-school vaccine coverage, no within-school NPIs, and predominant circulation of the Delta variant), we estimated that an elementary school could see 33–65 additional symptomatic cases of COVID-19 over a four-month semester (depending on the relative susceptibility of children <10 years). In contrast, under the Bay Area reopening plan (universal mask use, community and school vaccination coverage of 70%), we estimated excess symptomatic infection attributable to school reopening among 2.0–9.7% of elementary students (8–36 excess symptomatic cases per school over the semester), 3.0% of middle school students (13 cases per school) and 0.4% of high school students (3 cases per school). Excess rates among teachers attributable to reopening were similar. Achievement of lower risk tolerances, such as <5 excess infections per 1,000 students or teachers, required a cohort approach in elementary and middle school populations. In the absence of NPIs, increasing the vaccination coverage of community members from 50% to 70% or elementary teachers from 70% to 95% reduced the estimated excess rate of infection among elementary school students attributable to school transmission by 24% and 41%, respectively. We estimated that with 70% coverage of the eligible community and school population with a vaccine that is ≤65% effective, universal masking can avert more cases than masking of unvaccinated persons alone. CONCLUSIONS: Amidst circulation of the Delta variant, our findings demonstrated that schools are not inherently low risk, yet can be made so with high community vaccination coverages and universal masking. Vaccination of adult community members and teachers protects unvaccinated elementary and middle school children. Elementary and middle schools that can support additional interventions, such as cohorts and testing, should consider doing so, particularly if additional studies find that younger children are equally as susceptible as adults to the Delta variant of SARS-CoV-2. LIMITATIONS: We did not consider the effect of social distancing in classrooms, or variation in testing frequency, and considerable uncertainty remains in key transmission parameters.

medRxiv2021       CORD-19
8366Evaluation of an Automated High-Throughput Liquid-Based RNA Extraction Platform on Pooled Nasopharyngeal or Saliva Specimens for SARS-CoV-2 RT-PCR  

SARS-CoV-2 RT-PCR with pooled specimens has been implemented during the COVID-19 pandemic as a cost- and manpower-saving strategy for large-scale testing. However, there is a paucity of data on the efficiency of different nucleic acid extraction platforms on pooled specimens. This study compared a novel automated high-throughput liquid-based RNA extraction (LRE) platform (PHASIFY™) with a widely used magnetic bead-based total nucleic acid extraction (MBTE) platform (NucliSENS(®) easyMAG(®)). A total of 60 pools of nasopharyngeal swab and 60 pools of posterior oropharyngeal saliva specimens, each consisting of 1 SARS-CoV-2 positive and 9 SARS-CoV-2 negative specimens, were included for the comparison. Real-time RT-PCR targeting the SARS-CoV-2 RdRp/Hel gene was performed, and GAPDH RT-PCR was used to detect RT-PCR inhibitors. No significant differences were observed in the Ct values and overall RT-PCR positive rates between LRE and MBTE platforms (92.5% (111/120] vs. 90% (108/120]), but there was a slightly higher positive rate for LRE (88.3% (53/60]) than MBTE (81.7% (49/60]) among pooled saliva. The automated LRE method is comparable to a standard MBTE method for the detection of SAR-CoV-2 in pooled specimens, providing a suitable alternative automated extraction platform. Furthermore, LRE may be better suited for pooled saliva specimens due to more efficient removal of RT-PCR inhibitors.

Viruses2021       LitCov and CORD-19
8367Development and validation of a questionnaire to assess knowledge, attitude, practices and concerns regarding COVID-19 vaccination among the general population  

BACKGROUND AND AIMS: There seems to be hesitation in the general population in accepting COVID 19 vaccine because of associated myths and/or misinformation. This study is dedicated to develop and validate a tool to interpret vaccine acceptance and/or hesitancy by assessing the knowledge, attitude, practices, and concerns regarding the COVID vaccine. MATERIAL AND METHODS: Mixed methods study design was used. In phase 1, the questionnaire was developed through literature review, focus group discussion, expert evaluation, and pre-testing. In phase 2, the validity of the questionnaire was obtained by conducting a cross-sectional survey on 201 participants. The construct validity was established via principal component analysis. Cronbach's alpha value was used to assess the reliability of the questionnaire. RESULTS: The 39-item questionnaire to assess the knowledge, attitude, practices, and concerns regarding the COVID-19 vaccine was developed. The Cronbach's alpha value of the questionnaire was 0.86 suggesting a good internal consistency. CONCLUSION: The developed tool is valid to assess the knowledge, attitude, practices and concerns regarding the COVID-19 vaccine acceptance and/or hesitancy. It has the potential utility for healthcare workers and government authorities to further build vaccine literacy.

Diabetes Metab Syndr2021       LitCov and CORD-19
8368Systematic review of artificial intelligence techniques in the detection and classification of COVID-19 medical images in terms of evaluation and benchmarking: Taxonomy analysis, challenges, future solutions and methodological aspects  

This study presents a systematic review of artificial intelligence (AI) techniques used in the detection and classification of coronavirus disease 2019 (COVID-19) medical images in terms of evaluation and benchmarking. Five reliable databases, namely, IEEE Xplore, Web of Science, PubMed, ScienceDirect and Scopus were used to obtain relevant studies of the given topic. Several filtering and scanning stages were performed according to the inclusion/exclusion criteria to screen the 36 studies obtained; however, only 11 studies met the criteria. Taxonomy was performed, and the 11 studies were classified on the basis of two categories, namely, review and research studies. Then, a deep analysis and critical review were performed to highlight the challenges and critical gaps outlined in the academic literature of the given subject. Results showed that no relevant study evaluated and benchmarked AI techniques utilised in classification tasks (i.e. binary, multi-class, multi-labelled and hierarchical classifications) of COVID-19 medical images. In case evaluation and benchmarking will be conducted, three future challenges will be encountered, namely, multiple evaluation criteria within each classification task, trade-off amongst criteria and importance of these criteria. According to the discussed future challenges, the process of evaluation and benchmarking AI techniques used in the classification of COVID-19 medical images considered multi-complex attribute problems. Thus, adopting multi-criteria decision analysis (MCDA) is an essential and effective approach to tackle the problem complexity. Moreover, this study proposes a detailed methodology for the evaluation and benchmarking of AI techniques used in all classification tasks of COVID-19 medical images as future directions; such methodology is presented on the basis of three sequential phases. Firstly, the identification procedure for the construction of four decision matrices, namely, binary, multi-class, multi-labelled and hierarchical, is presented on the basis of the intersection of evaluation criteria of each classification task and AI classification techniques. Secondly, the development of the MCDA approach for benchmarking AI classification techniques is provided on the basis of the integrated analytic hierarchy process and VlseKriterijumska Optimizacija I Kompromisno Resenje methods. Lastly, objective and subjective validation procedures are described to validate the proposed benchmarking solutions.

J Infect Public Health2020       LitCov and CORD-19
8369Increased Incidence of In-Hospital Ischemic Stroke During SARS-CoV-2 Outbreak: A Single-Center Study  

BACKGROUND: Meta-analyses of observational studies report a 1.1–1.7% pooled risk of stroke among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring hospitalization, but consultations for stroke and reperfusion procedures have decreased during the outbreak that occurred during the first half of the year 2020. It is still unclear whether a true increase in the risk of stroke exists among patients with coronavirus disease 2019 (COVID-19). In-hospital ischemic stroke (IHIS) complicated the 0.04–0.06% of all admissions in the pre-COVID-19 era, but its incidence has not been assessed among inpatients with COVID-19. We aimed to compare IHIS incidence among patients with SARS-CoV-2 infection with that of inpatients with non-COVID-19 illnesses from the same outbreak period and from previous periods. METHODS: This historical cohort study belongs to the COVID-19@Vallecas cohort. The incidence of IHIS was estimated for patients with SARS-CoV-2 hospitalized during March–April 2020 [COVID-19 cohort (CC)], for patients with non-COVID-19 medical illness hospitalized during the same outbreak period [2020 non-COVID-19 cohort (20NCC)], and for inpatients with non-COVID-19 illness admitted during March–April of the years 2016–2019 [historical non-COVID-19 cohort (HNCC)]. Unadjusted risk of IHIS was compared between the three cohorts, and adjusted incidence rate ratio (IRR) of IHIS between cohorts was obtained by means of Poisson regression. RESULTS: Overall, 8126 inpatients were included in this study. Patients in the CC were younger and more commonly men than those from the HNCC and 20NCC. Absolute risk of IHIS was 0.05% for HNCC, 0.23% for 20NCC, and 0.36% for CC, (p = 0.004 for HNCC vs. CC). Cumulative incidence for IHIS by day nine after admission, with death as a competing risk, was 0.09% for HNCC, 0.23% for 20NCC, and 0.50% for CC. In an adjusted Poisson regression model with sex, age, needing of intensive care unit admission, and cohort (HNCC as reference) as covariates, COVID-19 was an independent predictor for IHIS (IRR 6.76, 95% confidence interval 1.66–27.54, p = 0.01). A nonsignificant increase in the risk of IHIS was observed for the 20NCC (IRR 5.62, 95% confidence interval 0.93–33.9, p = 0.06). CONCLUSIONS: SARS-CoV-2 outbreak was associated with an increase in the incidence of IHIS when compared with inpatients from a historical cohort. Viral infection itself may be related to the increased risk of IHIS among patients with COVID-19, but in view of our results from the 20NCC, it is likely that other factors, such as hospital saturation and overwhelming of health systems, may have played a role in the increased frequency of IHIS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12028-021-01286-1.

Neurocrit Care2021       LitCov and CORD-19
8370Comparison of In Situ Hybridization, Immunohistochemistry and Reverse Transcription-Droplet Digital PCR for SARS-CoV-2 Testing in Tissue  

N/A

Arch Pathol Lab Med2021       LitCov and CORD-19
8371SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans  

N/A

Nature2021       LitCov and CORD-19
8372Rapid Implementation and Innovative Applications of a Virtual Intensive Care Unit During the COVID-19 Pandemic: Case Study  

BACKGROUND: The COVID-19 pandemic has necessitated a rapid increase of space in highly infectious disease intensive care units (ICUs). At Houston Methodist Hospital (HMH), a virtual intensive care unit (vICU) was used amid the COVID-19 outbreak. OBJECTIVE: The aim of this paper was to detail the novel adaptations and rapid expansion of the vICU that were applied to achieve patient-centric solutions while protecting staff and patients’ families during the pandemic. METHODS: The planned vICU implementation was redirected to meet the emerging needs of conversion of COVID-19 ICUs, including alterations to staged rollout timing, virtual and in-person staffing, and scope of application. With the majority of the hospital critical care physician workforce redirected to rapidly expanded COVID-19 ICUs, the non–COVID-19 ICUs were managed by cardiovascular surgeons, cardiologists, neurosurgeons, and acute care surgeons. HMH expanded the vICU program to fill the newly depleted critical care expertise in the non–COVID-19 units to provide urgent, emergent, and code blue support to all ICUs. RESULTS: Virtual family visitation via the Consultant Bridge application, palliative care delivery, and specialist consultation for patients with COVID-19 exemplify the successful adaptation of the vICU implementation. Patients with COVID-19, who were isolated and separated from their families to prevent the spread of infection, were able to virtually see and hear their loved ones, which bolstered the mental and emotional status of those patients. Many families expressed gratitude for the ability to see and speak with their loved ones. The vICU also protected medical staff and specialists assigned to COVID-19 units, reducing exposure and conserving personal protective equipment. CONCLUSIONS: Telecritical care has been established as an advantageous mechanism for the delivery of critical care expertise during the expedited rollout of the vICU at Houston Methodist Hospital. Overall responses from patients, families, and physicians are in favor of continued vICU care; however, further research is required to examine the impact of innovative applications of telecritical care in the treatment of critically ill patients.

J Med Internet Res2020       LitCov and CORD-19
8373Wearing one for the team: views and attitudes to face covering in New Zealand/Aotearoa during COVID-19 Alert Level 4 lockdown  

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J Prim Healthcare2020       LitCov and CORD-19
8374Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial  

BACKGROUND: To mitigate the effects of COVID-19, a vaccine is urgently needed. BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) or alum (Algel). METHODS: We did a double-blind, multicentre, randomised, controlled phase 1 trial to assess the safety and immunogenicity of BBV152 at 11 hospitals across India. Healthy adults aged 18–55 years who were deemed healthy by the investigator were eligible. Individuals with positive SARS-CoV-2 nucleic acid and/or serology tests were excluded. Participants were randomly assigned to receive either one of three vaccine formulations (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) or an Algel only control vaccine group. Block randomisation was done with a web response platform. Participants and investigators were masked to treatment group allocation. Two intramuscular doses of vaccines were administered on day 0 (the day of randomisation) and day 14. Primary outcomes were solicited local and systemic reactogenicity events at 2 h and 7 days after vaccination and throughout the full study duration, including serious adverse events. Secondary outcome was seroconversion (at least four-fold increase from baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot. The trial is registered at ClinicalTrials.gov (NCT04471519). FINDINGS: Between July 13 and 30, 2020, 827 participants were screened, of whom 375 were enrolled. Among the enrolled participants, 100 each were randomly assigned to the three vaccine groups, and 75 were randomly assigned to the control group (Algel only). After both doses, solicited local and systemic adverse reactions were reported by 17 (17%; 95% CI 10·5–26·1) participants in the 3 μg with Algel-IMDG group, 21 (21%; 13·8–30·5) in the 6 μg with Algel-IMDG group, 14 (14%; 8·1–22·7) in the 6 μg with Algel group, and ten (10%; 6·9–23·6) in the Algel-only group. The most common solicited adverse events were injection site pain (17 [5%] of 375 participants), headache (13 [3%]), fatigue (11 [3%]), fever (nine [2%]), and nausea or vomiting (seven [2%]). All solicited adverse events were mild (43 [69%] of 62) or moderate (19 [31%]) and were more frequent after the first dose. One serious adverse event of viral pneumonitis was reported in the 6 μg with Algel group, unrelated to the vaccine. Seroconversion rates (%) were 87·9, 91·9, and 82·8 in the 3 μg with Algel-IMDG, 6 μg with Algel-IMDG, and 6 μg with Algel groups, respectively. CD4(+) and CD8(+) T-cell responses were detected in a subset of 16 participants from both Algel-IMDG groups. INTERPRETATION: BBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted. FUNDING: Bharat Biotech International.

Lancet Infect Dis2021       LitCov and CORD-19
8375Estimating the effect of non-pharmaceutical interventions to mitigate COVID-19 spread in Saudi Arabia  

BACKGROUND: The Kingdom of Saudi Arabia (KSA) quickly controlled the spread of SARS-CoV-2 by implementing several non-pharmaceutical interventions (NPIs), including suspension of international and national travel, local curfews, closing public spaces (i.e., schools and universities, malls and shops), and limiting religious gatherings. The KSA also mandated all citizens to respect physical distancing and to wear face masks. However, after relaxing some restrictions during June 2020, the KSA is now planning a strategy that could allow resuming in-person education and international travel. The aim of our study was to evaluate the effect of NPIs on the spread of the COVID-19 and test strategies to open schools and resume international travel. METHODS: We built a spatial-explicit individual-based model to represent the whole KSA population (IBM-KSA). The IBM-KSA was parameterized using country demographic, remote sensing, and epidemiological data. A social network was created to represent contact heterogeneity and interaction among age groups of the population. The IBM-KSA also simulated the movement of people across the country based on a gravity model. We used the IBM-KSA to evaluate the effect of different NPIs adopted by the KSA (physical distancing, mask-wearing, and contact tracing) and to forecast the impact of strategies to open schools and resume international travels. RESULTS: The IBM-KSA results scenarios showed the high effectiveness of mask-wearing, physical distancing, and contact tracing in controlling the spread of the disease. Without NPIs, the KSA could have reported 4,824,065 (95% CI: 3,673,775–6,335,423) cases by June 2021. The IBM-KSA showed that mandatory mask-wearing and physical distancing saved 39,452 lives (95% CI: 26,641–44,494). In-person education without personal protection during teaching would have resulted in a high surge of COVID-19 cases. Compared to scenarios with no personal protection, enforcing mask-wearing and physical distancing in schools reduced cases, hospitalizations, and deaths by 25% and 50%, when adherence to these NPIs was set to 50% and 70%, respectively. The IBM-KSA also showed that a quarantine imposed on international travelers reduced the probability of outbreaks in the country. CONCLUSIONS: This study showed that the interventions adopted by the KSA were able to control the spread of SARS-CoV-2 in the absence of a vaccine. In-person education should be resumed only if NPIs could be applied in schools and universities. International travel can be resumed but with strict quarantine rules. The KSA needs to keep strict NPIs in place until a high fraction of the population is vaccinated in order to reduce hospitalizations and deaths. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02232-4.

BMC Med2022       LitCov and CORD-19
8376Immune Memory in Mild COVID-19 Patients and Unexposed Donors Reveals Persistent T Cell Responses After SARS-CoV-2 Infection  

Understanding the causes of the diverse outcome of COVID-19 pandemic in different geographical locations is important for the worldwide vaccine implementation and pandemic control responses. We analyzed 42 unexposed healthy donors and 28 mild COVID-19 subjects up to 5 months from the recovery for SARS-CoV-2 specific immunological memory. Using HLA class II predicted peptide megapools, we identified SARS-CoV-2 cross-reactive CD4(+) T cells in around 66% of the unexposed individuals. Moreover, we found detectable immune memory in mild COVID-19 patients several months after recovery in the crucial arms of protective adaptive immunity; CD4(+) T cells and B cells, with a minimal contribution from CD8(+) T cells. Interestingly, the persistent immune memory in COVID-19 patients is predominantly targeted towards the Spike glycoprotein of the SARS-CoV-2. This study provides the evidence of both high magnitude pre-existing and persistent immune memory in Indian population. By providing the knowledge on cellular immune responses to SARS-CoV-2, our work has implication for the development and implementation of vaccines against COVID-19.

Front Immunol2021       LitCov and CORD-19
8377Placental SARS-CoV-2 in a pregnant woman with mild COVID-19 disease  

BACKGROUND: The full impact of COVID‐19 on pregnancy remains uncharacterized. Current literature suggests minimal maternal, fetal, and neonatal morbidity and mortality.(1) COVID‐19 manifestations appear similar between pregnant and non‐pregnant women.(2) OBJECTIVES/STUDY DESIGN: We present a case of placental SARS‐CoV‐2 virus in a woman with mild COVID‐19 disease, then review the literature. RT‐PCR was performed to detect SARS‐CoV‐2. Immunohistochemistry staining was performed with specific monoclonal antibodies to detect SARS‐CoV‐2 antigen or to identify trophoblasts. RESULTS: A 29 year‐old multigravida presented at 40‐4/7 weeks for labor induction. With myalgias two days prior, she tested positive for SARS‐CoV‐2. We demonstrate maternal vascular malperfusion, with no fetal vascular malperfusion, as well as SARS‐CoV‐2 virus in chorionic villi endothelial cells, and also rarely in trophoblasts. CONCLUSIONS: To our knowledge, this is the first report of placental SARS‐CoV‐2 despite mild COVID‐19 disease (no symptoms of COVID‐19 aside from myalgias); patient had no fever, cough, or shortness of breath, but only myalgias and sick contacts. Despite her mild COVID‐19 disease in pregnancy, we demonstrate placental vasculopathy and presence of SARS‐CoV‐2 virus across the placenta. Evidence of placental COVID‐19 raises concern for placental vasculopathy (potentially leading to fetal growth restriction and other pregnancy complications) and possible vertical transmission – especially for pregnant women who may be exposed to COVID‐19 in early pregnancy. This raises important questions of whether future pregnancy guidance should include stricter pandemic precautions, such as screening for a wider array of COVID‐19 symptoms, increased antenatal surveillance, and possibly routine COVID‐19 testing throughout pregnancy. This article is protected by copyright. All rights reserved.

J Med Virol2020       LitCov and CORD-19
8378How Shenzhen, China avoided widespread community transmission: a potential model for successful prevention and control of COVID-19  

Shenzhen is a city of 22 million people in south China that serves as a financial and trade center for East Asia. The city has extensive ties to Hubei Province, the first reported epicenter of the coronavirus disease 2019 (COVID-19) outbreak in the world. Initial predictions suggested Shenzhen would experience a high number of COVID-19 cases. These predictions have not materialized. As of 31 March 2020 Shenzhen had only 451 confirmed cases of COVID-19. Contact tracing has shown that no cases were the result of community transmission within the city. While Shenzhen did not implement a citywide lockdown like Wuhan, it did put into place a rapid response system first developed after the severe acute respiratory syndrome (SARS) epidemic in 2003. In the wake of the 2003 SARS outbreak, Shenzhen health authority created a network for surveillance and responding to novel respiratory infections, including pneumonia of unknown causes (PUC). The network rapidly detected mass discussion about PUC and immediately deployed emergency preparedness, quarantine for close contacts of PUC. Five early actions (early detection, early reporting, early diagnosis, early isolation, and early treatment) and four centralized responses (centralized coordination by experts, centralized allocation of resources, centralized placement of patients, and centralized provision of treatment) ensured effective prevention and control. Tripartite working teams comprising community cadres, medical personnel and police were formulated to conduct contact tracing at each neighborhood and residential community. Incorporation of mobile technology, big data, and artificial intelligence into COVID-19 response increased accessibility to health services, reduced misinformation and minimized the impact of fake news. Shenzhen’s unique experience in successfully controlling the COVID-19 outbreak may be a useful model for countries and regions currently experiencing rapid spread of the virus.

Infect Dis Poverty2020       LitCov and CORD-19
8379What is the effect of social distancing on the course of COVID-19 epidemic?  

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Pol Merkur Lekarski2021       LitCov and CORD-19
8380Type 2 Diabetes and COVID-19-Related Mortality in the Critical Care Setting: A National Cohort Study in England, March-July 2020  

OBJECTIVE: To describe the relationship between type 2 diabetes and all-cause mortality among adults with coronavirus disease 2019 (COVID-19) in the critical care setting. RESEARCH DESIGN AND METHODS: This was a nationwide retrospective cohort study in people admitted to hospital in England with COVID-19 requiring admission to a high dependency unit (HDU) or intensive care unit (ICU) between 1 March 2020 and 27 July 2020. Cox proportional hazards models were used to estimate 30-day in-hospital all-cause mortality associated with type 2 diabetes, with adjustment for age, sex, ethnicity, obesity, and other major comorbidities (chronic respiratory disease, asthma, chronic heart disease, hypertension, immunosuppression, chronic neurological disease, chronic renal disease, and chronic liver disease). RESULTS: A total of 19,256 COVID-19–related HDU and ICU admissions were included in the primary analysis, including 13,809 HDU (mean age 70 years) and 5,447 ICU (mean age 58 years) admissions. Of those admitted, 3,524 (18.3%) had type 2 diabetes and 5,077 (26.4%) died during the study period. Patients with type 2 diabetes were at increased risk of death (adjusted hazard ratio [aHR] 1.23 [95% CI 1.14, 1.32]), and this result was consistent in HDU and ICU subsets. The relative mortality risk associated with type 2 diabetes decreased with higher age (age 18–49 years aHR 1.50 [95% CI 1.05, 2.15], age 50–64 years 1.29 [1.10, 1.51], and age ≥65 years 1.18 [1.09, 1.29]; P value for age–type 2 diabetes interaction = 0.002). CONCLUSIONS: Type 2 diabetes may be an independent prognostic factor for survival in people with severe COVID-19 requiring critical care treatment, and in this setting the risk increase associated with type 2 diabetes is greatest in younger people.

Diabetes Care2020       LitCov and CORD-19
8381A Comprehensive Study of Artificial Intelligence and Machine Learning Approaches in Confronting the Coronavirus Pandemic  

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Int J Health Serv2021       LitCov and CORD-19
8382Health, psychosocial and economic impacts of the COVID-19 pandemic on people with chronic conditions in India: a mixed methods study  

BACKGROUND: People with chronic conditions are disproportionately prone to be affected by the COVID-19 pandemic but there are limited data documenting this. We aimed to assess the health, psychosocial and economic impacts of the COVID-19 pandemic on people with chronic conditions in India. METHODS: Between July 29, to September 12, 2020, we telephonically surveyed adults (n = 2335) with chronic conditions across four sites in India. Data on participants’ demographic, socio-economic status, comorbidities, access to health care, treatment satisfaction, self-care behaviors, employment, and income were collected using pre-tested questionnaires. We performed multivariable logistic regression analysis to examine the factors associated with difficulty in accessing medicines and worsening of diabetes or hypertension symptoms. Further, a diverse sample of 40 participants completed qualitative interviews that focused on eliciting patient’s experiences during the COVID-19 lockdowns and data analyzed using thematic analysis. RESULTS: One thousand seven hundred thirty-four individuals completed the survey (response rate = 74%). The mean (SD) age of respondents was 57.8 years (11.3) and 50% were men. During the COVID-19 lockdowns in India, 83% of participants reported difficulty in accessing healthcare, 17% faced difficulties in accessing medicines, 59% reported loss of income, 38% lost jobs, and 28% reduced fruit and vegetable consumption. In the final-adjusted regression model, rural residence (OR, 95%CI: 4.01,2.90–5.53), having diabetes (2.42, 1.81–3.25) and hypertension (1.70,1.27–2.27), and loss of income (2.30,1.62–3.26) were significantly associated with difficulty in accessing medicines. Further, difficulties in accessing medicines (3.67,2.52–5.35), and job loss (1.90,1.25–2.89) were associated with worsening of diabetes or hypertension symptoms. Qualitative data suggest most participants experienced psychosocial distress due to loss of job or income and had difficulties in accessing in-patient services. CONCLUSION: People with chronic conditions, particularly among poor, rural, and marginalized populations, have experienced difficulties in accessing healthcare and been severely affected both socially and financially by the COVID-19 pandemic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-10708-w.

BMC Public Health2021       LitCov and CORD-19
8383Continuing vs suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with SARS-CoV-2-The BRACE CORONA Trial  

BACKGROUND: Angiotensin-converting enzyme-2 (ACE2) may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19. The impact of discontinuing ACEI and ARBs in patients with COVID-19 remains uncertain. DESIGN BRACE CORONA is a pragmatic, multicenter, randomized, phase IV, clinical trial that aims to enroll around 500 participants at 32 sites in Brazil. Participants will be identified from an ongoing national registry of suspected and confirmed cases of COVID-19. Eligible patients using renin-angiotensin system blockers (ACEI/ARBs) with a confirmed diagnosis of COVID-19 will be randomized to a strategy of continued ACEI/ARB treatment versus temporary discontinuation for 30 days. The primary outcome is the median days alive and out of the hospital at 30 days. Secondary outcomes include progression of COVID-19 disease, all-cause mortality, death from vascular causes, myocardial infarction, stroke, transient ischemic attack, new or worsening heart failure, myocarditis, pericarditis, arrhythmias, thromboembolic events, hypertensive crisis, respiratory failure, hemodynamic decompensation, sepsis, renal failure, troponin, B-type natriuretic peptide, N-terminal-pro hormone and D-dimer levels. SUMMARY: BRACE CORONA will evaluate whether the strategy of continued ACEI/ARB therapy compared with temporary discontinuation of these drugs impacts clinical outcomes among patients with COVID-19.

Am Heart J2020       LitCov and CORD-19
8384Managing critical care during COVID-19 pandemic: The experience of an ICU of a tertiary care hospital  

BACKGROUND: The COVID-19 pandemic has strained ICUs worldwide. To learn from our experience, we described the critical care response to the outbreak. METHODS: This is a case study of the response of the Intensive Care Department (75-bed capacity) at a tertiary-care hospital to COVID-19 pandemic, which resulted in a high number of critically ill patients. RESULTS: Between March 1 and July 31, 2020, 822 patients were admitted to the adult non-cardiac ICUs with suspected (72%)/confirmed (38%) COVID-19. At the peak of the surge, 125 critically ill patients with COVID-19 were managed on single day. To accommodate these numbers, the bed capacity of 4 ICUs was increased internally from 58 to 71 beds (+40%) by cohorting 2 patients/room in selected rooms; forty additional ICUs beds were created in 2 general wards; one cardiac ICU was converted to managed non-COVID-19 general ICU patients and one ward was used as a stepdown for COVID-19 patients. To manage respiratory failure, 53 new ICU ventilators, 90 helmets for non-invasive ventilation and 47 high-flow nasal cannula machines were added to the existing capacity. Dedicated medical teams cared for the COVID-19 patients to prevent cross-contamination. The nurse-to-patient and RT-to-patient ratio remained mostly 1:1 and 1:6, respectively. One-hundred-ten ward nurses were up-skilled to care for COVID-19 and other ICU patients using tiered staffing model. Daily executive rounds were conducted to identify patients for transfer and at least 10 beds were made available for new COVID-19 admissions/day. The consumption of PPE increased multiple fold compared with the period preceding the pandemic. Regular family visits were not allowed and families were updated daily by videoconferencing and phone calls. CONCLUSIONS: Our ICU response to the COVID-19 pandemic required almost doubling ICU bed capacity and changing multiple aspects of ICU workflow to be able to care for high numbers of affected patients.

J Infect Public Health2021       LitCov and CORD-19
8385Excess years of life lost to COVID-19 and other causes of death by sex, neighbourhood deprivation and region in England and Wales during 2020: A registry-based study  

BACKGROUND: Deaths in the first year of the Coronavirus Disease 2019 (COVID-19) pandemic in England and Wales were unevenly distributed socioeconomically and geographically. However, the full scale of inequalities may have been underestimated to date, as most measures of excess mortality do not adequately account for varying age profiles of deaths between social groups. We measured years of life lost (YLL) attributable to the pandemic, directly or indirectly, comparing mortality across geographic and socioeconomic groups. METHODS AND FINDINGS: We used national mortality registers in England and Wales, from 27 December 2014 until 25 December 2020, covering 3,265,937 deaths. YLLs (main outcome) were calculated using 2019 single year sex-specific life tables for England and Wales. Interrupted time-series analyses, with panel time-series models, were used to estimate expected YLL by sex, geographical region, and deprivation quintile between 7 March 2020 and 25 December 2020 by cause: direct deaths (COVID-19 and other respiratory diseases), cardiovascular disease and diabetes, cancer, and other indirect deaths (all other causes). Excess YLL during the pandemic period were calculated by subtracting observed from expected values. Additional analyses focused on excess deaths for region and deprivation strata, by age-group. Between 7 March 2020 and 25 December 2020, there were an estimated 763,550 (95% CI: 696,826 to 830,273) excess YLL in England and Wales, equivalent to a 15% (95% CI: 14 to 16) increase in YLL compared to the equivalent time period in 2019. There was a strong deprivation gradient in all-cause excess YLL, with rates per 100,000 population ranging from 916 (95% CI: 820 to 1,012) for the least deprived quintile to 1,645 (95% CI: 1,472 to 1,819) for the most deprived. The differences in excess YLL between deprivation quintiles were greatest in younger age groups; for all-cause deaths, a mean of 9.1 years per death (95% CI: 8.2 to 10.0) were lost in the least deprived quintile, compared to 10.8 (95% CI: 10.0 to 11.6) in the most deprived; for COVID-19 and other respiratory deaths, a mean of 8.9 years per death (95% CI: 8.7 to 9.1) were lost in the least deprived quintile, compared to 11.2 (95% CI: 11.0 to 11.5) in the most deprived. For all-cause mortality, estimated deaths in the most deprived compared to the most affluent areas were much higher in younger age groups, but similar for those aged 85 or over. There was marked variability in both all-cause and direct excess YLL by region, with the highest rates in the North West. Limitations include the quasi-experimental nature of the research design and the requirement for accurate and timely recording. CONCLUSIONS: In this study, we observed strong socioeconomic and geographical health inequalities in YLL, during the first calendar year of the COVID-19 pandemic. These were in line with long-standing existing inequalities in England and Wales, with the most deprived areas reporting the largest numbers in potential YLL.

PLoS Med2022       LitCov and CORD-19
8386IgG antibody titers against SARS-CoV-2 nucleocapsid protein correlate with the severity of COVID-19 patients  

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) is a current worldwide threat for which the immunological features after infection need to be investigated. The aim of this study was to establish a highly sensitive and quantitative detection method for SARS-CoV-2 IgG antibody and to compare the antibody reaction difference in patients with different disease severity. RESULTS: Recombinant SARS-CoV-2 nucleocapsid protein was expressed in Escherichia coli and purified to establish an indirect IgG ELISA detection system. The sensitivity of the ELISA was 100% with a specificity of 96.8% and a 98.3% concordance when compared to a colloidal gold kit, in addition, the sensitivity of the ELISA was 100% with a specificity of 98.9% and a 99.4% concordance when compared to a SARS-CoV-2 spike S1 protein IgG antibody ELISA kit. The increased sensitivity resulted in a higher rate of IgG antibody detection for COVID-19 patients. Moreover, the quantitative detection can be conducted with a much higher serum dilution (1:400 vs 1:10, 1:400 vs 1:100). The antibody titers of 88 patients with differing COVID-19 severity at their early convalescence ranged from 800 to 102,400, and the geometric mean titer for severe and critical cases, moderate cases, asymptomatic and mild cases was 51,203, 20,912, and 9590 respectively. CONCLUSION: The development of a highly sensitive ELISA system for the detection of SARS-CoV-2 IgG antibodies is described herein. This system enabled a quantitative study of rSARS-CoV-2-N IgG antibody titers in COVID-19 patients, the occurrence of higher IgG antibody titers were found to be correlated with more severe cases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-021-02401-0.

BMC Microbiol2021       LitCov and CORD-19
8387Genomic Surveillance of Circulating SARS-CoV-2 in South East Italy: A One-Year Retrospective Genetic Study  

In order to provide insights into the evolutionary and epidemiological viral dynamics during the current COVID-19 pandemic in South Eastern Italy, a total of 298 genomes of SARS-CoV-2 strains collected in the Apulia and Basilicata regions, between March 2020 and January 2021, were sequenced. The genomic analysis performed on the draft genomes allowed us to assign the genetic clades and lineages of belonging to each sample and provide an overview of the main circulating viral variants. Our data showed the spread in Apulia and Basilicata of SARS-CoV-2 variants which have emerged during the second wave of infections and are being currently monitored worldwide for their increased transmission rate and their possible impact on vaccines and therapies. These results emphasize the importance of genome sequencing for the epidemiological surveillance of the new SARS-CoV-2 variants’ spread.

Viruses2021       LitCov and CORD-19
8388Eating Habits during the COVID-19 Lockdown in Italy: The Nutritional and Lifestyle Side Effects of the Pandemic  

To limit the spread of coronavirus SARS-CoV-2, a nationwide lockdown started in Italy in March 2020. In this unpredictable situation, a cross-sectional study using an online questionnaire was carried out by the Observatory on Food Surplus, Recovery and Waste of CREA Food and Nutrition Centre. The aim of this work was to evaluate how Italian habits changed during this period, the determinants of changes, and the effect on food waste prevention. In a sample of 2678 respondents, 62% showed low Adherence to the Mediterranean Diet (AMD). During lockdown many of participants improved the quality of their diet, increasing their consumption of fruit (24.4%), vegetables (28.5%), legumes (22.1%), nuts (12%), and fish or shellfish (14%). Unfavorable changes were observed with the excessive consumption of sweets or pastries (36.9%) and comfort foods (22.7%), and a lack of physical activity (37.2%). The main novelty of this study was the examination of dietary changes identified by a cluster analysis. Respondents with generally high AMD improved their eating habits, while the habits of the respondents with generally low AMD remained unchanged. In addition, nearly 80% of respondents were sensitive to food waste. The study provides a useful contribution to the debate on nutritional recommendations in case of further lockdown.

Nutrients2021       LitCov and CORD-19
8389The Transition of Academic Mental Health Clinics to Telehealth During the COVID-19 Pandemic  

OBJECTIVE: A consortium of 8 academic child and adolescent psychiatry programs in the United States and Canada examined their pivot from in-person, clinic-based services to home-based telehealth during the COVID-19 pandemic. The aims were to document the transition across diverse sites and to present recommendations for future telehealth service planning. METHOD: Consortium sites completed a Qualtrics survey assessing site characteristics, telehealth practices, service use, and barriers to and facilitators of telehealth service delivery prior to (pre) and during the early stages of (post) the COVID-19 pandemic. The design is descriptive. RESULTS: All sites pivoted from in-person services to home-based telehealth within 2 weeks. Some sites experienced delays in conducting new intakes, and most experienced delays establishing tele−group therapy. No-show rates and use of telephony versus videoconferencing varied by site. Changes in telehealth practices (eg, documentation requirements, safety protocols) and perceived barriers to telehealth service delivery (eg, regulatory limitations, inability to bill) occurred pre−/post−COVID-19. CONCLUSION: A rapid pivot from in-person services to home-based telehealth occurred at 8 diverse academic programs in the context of a global health crisis. To promote ongoing use of home-based telehealth during future crises and usual care, academic programs should continue documenting the successes and barriers to telehealth practice to promote equitable and sustainable telehealth service delivery in the future.

J Am Acad Child Adolesc Psychi2021       LitCov and CORD-19
8390Myopericarditis following COVID-19 vaccination and non-COVID-19 vaccination: a systematic review and meta-analysis  

Background Myopericarditis is a rare complication of vaccination. However, there have been increasing reports of myopericarditis following COVID-19 vaccination, especially among adolescents and young adults. We aimed to characterise the incidence of myopericarditis following COVID-19 vaccination, and compare this with non-COVID-19 vaccination. Methods We did a systematic review and meta-analysis, searching four international databases from Jan 1, 1947, to Dec 31, 2021, for studies in English reporting on the incidence of myopericarditis following vaccination (the primary outcome). We included studies reporting on people in the general population who had myopericarditis in temporal relation to receiving vaccines, and excluded studies on a specific subpopulation of patients, non-human studies, and studies in which the number of doses was not reported. Random-effects meta-analyses (DerSimonian and Laird) were conducted, and the intra-study risk of bias (Joanna Briggs Institute checklist) and certainty of evidence (Grading of Recommendations, Assessment, Development and Evaluations approach) were assessed. We analysed the difference in incidence of myopericarditis among subpopulations, stratifying by the type of vaccine (COVID-19 vs non-COVID-19) and age group (adult vs paediatric). Among COVID-19 vaccinations, we examined the effect of the type of vaccine (mRNA or non-mRNA), sex, age, and dose on the incidence of myopericarditis. This study was registered with PROSPERO (CRD42021275477). Findings The overall incidence of myopericarditis from 22 studies (405 272 721 vaccine doses) was 33·3 cases (95% CI 15·3–72·6) per million vaccine doses, and did not differ significantly between people who received COVID-19 vaccines (18·2 [10·9–30·3], 11 studies [395 361 933 doses], high certainty) and those who received non-COVID-19 vaccines (56·0 [10·7–293·7], 11 studies [9 910 788 doses], moderate certainty, p=0·20). Compared with COVID-19 vaccination, the incidence of myopericarditis was significantly higher following smallpox vaccinations (132·1 [81·3–214·6], p<0·0001) but was not significantly different after influenza vaccinations (1·3 [0·0–884·1], p=0·43) or in studies reporting on various other non-smallpox vaccinations (57·0 [1·1–3036·6], p=0·58). Among people who received COVID-19 vaccines, the incidence of myopericarditis was significantly higher in males (vs females), in people younger than 30 years (vs 30 years or older), after receiving an mRNA vaccine (vs non-mRNA vaccine), and after a second dose of vaccine (vs a first or third dose). Interpretation The overall risk of myopericarditis after receiving a COVID-19 vaccine is low. However, younger males have an increased incidence of myopericarditis, particularly after receiving mRNA vaccines. Nevertheless, the risks of such rare adverse events should be balanced against the risks of COVID-19 infection (including myopericarditis). Funding None.

Lancet Respir Med2022       LitCov and CORD-19
8391Promoting Service Leadership Qualities and Well-Being among University Students through an Online Course during COVID-19 Pandemic  

The COVID-19 pandemic is a great challenge to leadership education in universities. Although previous findings provide support for the effectiveness of online learning, the impact of online leadership course on students’ learning outcomes and well-being has not been well documented. Using objective outcome and subjective outcome evaluation strategies, the present study examined students’ perceived qualities and effectiveness of an online credit-bearing service leadership course adopting asynchronous mode (primarily online learning) and synchronous mode under COVID-19. Regardless of teaching modes, the subject yielded positive impacts. Specifically, pretest-posttest (N = 228) showed that there were positive changes in students’ service leadership qualities, life satisfaction and psychological well-being. For students’ perception of the course (N = 219), results indicated that most students were positive in their learning experience and satisfied with course design, lecturer quality and the benefits of the course to their development. Students’ changes and subjective perceptions were positively correlated, but with a low effect size. The findings reflected that online service leadership course adopting asynchronous or synchronous mode was effective, and students were positive about their learning experience.

Int J Environ Res Public Healt2021       LitCov and CORD-19
8392Effects of the COVID-19 pandemic on primary care-recorded mental illness and self-harm episodes in the UK: a population-based cohort study  

BACKGROUND: The COVID-19 pandemic has adversely affected population mental health. We aimed to assess temporal trends in primary care-recorded common mental illness, episodes of self-harm, psychotropic medication prescribing, and general practitioner (GP) referrals to mental health services during the COVID-19 emergency in the UK. METHODS: We did a population-based cohort study using primary care electronic health records from general practices registered on the UK Clinical Practice Research Datalink (CPRD). We included patient records from Jan 1, 2010, to Sept 10, 2020, to establish long-term trends and patterns of seasonality, but focused primarily on the period January, 2019–September, 2020. We extracted data on clinical codes entered into patient records to estimate the incidence of depression and anxiety disorders, self-harm, prescriptions for antidepressants and benzodiazepines, and GP referrals to mental health services, and assessed event rates of all psychotropic prescriptions and self-harm. We used mean-dispersion negative binomial regression models to predict expected monthly incidence and overall event rates, which were then compared with observed rates to assess the percentage reduction in incidence and event rates after March, 2020. We also stratified analyses by sex, age group, and practice-level Index of Multiple Deprivation quintiles. FINDINGS: We identified 14 210 507 patients from 1697 UK general practices registered in the CPRD databases. In April, 2020, compared with expected rates, the incidence of primary care-recorded depression had reduced by 43·0% (95% CI 38·3–47·4), anxiety disorders by 47·8% (44·3–51·2), and first antidepressant prescribing by 36·4% (33·9–38·8) in English general practices. Reductions in first diagnoses of depression and anxiety disorders were largest for adults of working age (18–44 and 45–64 years) and for patients registered at practices in more deprived areas. The incidence of self-harm was 37·6% (34·8–40·3%) lower than expected in April, 2020, and the reduction was greatest for women and individuals aged younger than 45 years. By September, 2020, rates of incident depression, anxiety disorder, and self-harm were similar to expected levels. In Northern Ireland, Scotland, and Wales, rates of incident depression and anxiety disorder remained around a third lower than expected to September, 2020. In April, 2020, the rate of referral to mental health services was less than a quarter of the expected rate for the time of year (75·3% reduction [74·0–76·4]). INTERPRETATION: Consequences of the considerable reductions in primary care-recorded mental illness and self-harm could include more patients subsequently presenting with greater severity of mental illness and increasing incidence of non-fatal self-harm and suicide. Addressing the effects of future lockdowns and longer-term impacts of economic instability on mental health should be prioritised. FUNDING: National Institute for Health Research and Medical Research Council.

Lancet Public Health2021       LitCov and CORD-19
8393Buccal swabs as non-invasive specimens for detection of SARS-CoV-2  

INTRODUCTION: The current gold standard for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA involves subjecting nasopharyngeal or oropharyngeal swabs to reverse transcription quantitative PCR (RT-qPCR). However, both sample types need to be collected by trained professionals. Using self-collected buccal swabs as an alternative could simplify and accelerate diagnosis of coronavirus disease 2019 (COVID-19). OBJECTIVE: To assess self-collected buccal swab samples as an alternative method for SARS-CoV-2 detection in patients with COVID-19. METHODS: Buccal swab samples were self-collected by 73 patients with COVID-19. Total RNA was extracted using Qiagen kits. RNA encoding the SARS-CoV-2 Env protein and human RNase P as an internal control was amplified using the TRUPCR(®) SARS-CoV-2 RT-qPCR kit version 2.1 and a Bio-Rad CFX96 Real-Time Detection System. RESULT: The sensitivity of RT-qPCR from buccal swabs was 58.9% (43/73; 95% confidence interval [CI] 46.77%–70.27%) and that of RT-qPCR from saliva was 62.90% (39/62; 95% CI 49.69%–74.84%) taking positive SARS-CoV-2 RT-qPCR from nasopharyngeal swabs as the gold standard. CONCLUSION: Self-collected buccal swabs are promising alternatives to nasopharyngeal or oropharyngeal swabs for SARS CoV-2 detection.

J Int Med Res2021       LitCov and CORD-19
8394Mobile Apps Leveraged in the COVID-19 Pandemic in East and Southeast Asia: Review and Content Analysis  

BACKGROUND: The COVID-19 pandemic increased attention to digital tools to support governmental public health policies in East and South-East Asia. Mobile apps related to the COVID-19 pandemic continue to emerge and evolve with a wide variety of characteristics and functions. However, there is a paucity of studies evaluating such apps in this region, with most of the available studies conducted in the early days of the pandemic. OBJECTIVE: This study aimed to examine free apps developed or supported by governments in the East and South-East Asian region and highlight their key characteristics and functions. We also sought to interpret how the release dates of these apps were related to the commencement dates of other COVID-19 public health policies. METHODS: We systematically searched for apps in Apple App Store and Google Play Store and analyzed the contents of eligible apps. Mobile apps released or updated with COVID-19–related functions between March 1 and May 7, 2021, in Singapore, Taiwan, South Korea, China (mainland), Japan, Thailand, Hong Kong, Vietnam, Malaysia, Indonesia, and the Philippines were included. The CoronaNet Research Project database was also examined to determine the timeline of public health policy commencement dates in relation to the release dates of the included apps. We assessed each app’s official website, media reports, and literature through content analysis. Descriptive statistics were used to summarize relevant information gathered from the mobile apps using RStudio. RESULTS: Of the 1943 mobile apps initially identified, 46 were eligible, with almost 70% of the apps being intended for the general public. Most apps were from Vietnam (n=9, 20%), followed by Malaysia, Singapore, and Thailand (n=6 each, 13%). Of note, most apps for quarantine monitoring (n=6, 13%) were mandatory for the target users or a population subset. The most common function was health monitoring (32/46, 70%), followed by raising public health awareness (19/46, 41%) through education and information dissemination. Other functions included monitoring quarantine (12/46, 26%), providing health resources (12/46, 26%). COVID-19 vaccination management functions began to appear in parallel with vaccine rollout (7/46, 15%). Regarding the timing of the introduction of mobile solutions, the majority of mobile apps emerged close to the commencement dates of other public health policies in the early stages of the pandemic between March and April 2020. CONCLUSIONS: In East and South-East Asia, most governments used mobile health apps as adjuncts to public health measures for tracking COVID-19 cases and delivering credible information. In addition, these apps have evolved by expanding their functions for COVID-19 vaccination.

JMIR Mhealth Uhealth2021       LitCov and CORD-19
8395SARS-CoV-2 N gene dropout and N gene Ct value shift as indicator for the presence of B.1.1.7 lineage in a commercial multiplex PCR assay  

OBJECTIVES: Detection and surveillance of SARS-CoV-2 is of eminent importance, particularly due to the rapid emergence of variants of concern (VOCs). In this study we evaluated if commercially available quantitative real-time PCR (qRT-PCR) assay can identify SARS-CoV-2 B.1.1.7 lineage samples by a specific N gene dropout or Ct value shift compared to the S or RdRp gene. METHODS: VOC B.1.1.7 and non-B.1.1.7 SARS-CoV-2-positive patient samples were identified via whole-genome sequencing and variant-specific PCR. Confirmed B.1.1.7 (n=48) and non-B.1.1.7 samples (n=58) were analysed using the Allplex™ SARS-CoV-2/FluA/FluB/RSV™ PCR assay for presence of SARS-CoV-2 S, RdRp and N gene. N gene coding sequence of SARS-CoV-2 with and without D3L mutation (specific for B.1.1.7) was cloned into pCR®-TOPO vectors to validate polymorphism dependent N gene dropout with Allplex™ SARS-CoV-2/FluA/FluB/RSV™ PCR assay. RESULTS: All studied B.1.1.7-positive patient samples showed significantly higher Ct values in qRT-PCR (Δ 6-10, N gene dropout on Ct values >29) of N gene compared to the corresponding values of S (p ≤ 0.0001) and RdRp (p ≤ 0.0001) genes. The assay reliably discriminated B.1.1.7 and non-B.1.1.7 positive samples (area under the curve AUC = 1) in a receiver operating characteristic (ROC) curve analysis. Identical Ct shifts (Δ 7-10) were detected in reverse genetic experiments, using isolated plasmids containing N gene coding sequences corresponding to D3 or 3L variants. CONCLUSIONS: A N gene dropout or Ct value shift is shown for B.1.1.7-positive samples in the Allplex™ SARS-CoV-2/FluA/FluB/RSV PCR assay. This approach can be used as a rapid tool for B.1.1.7 detection in single assay high throughput diagnostics.

Clin Microbiol Infect2021       LitCov and CORD-19
8396Utility of telemedicine in the COVID-19 era  

N/A

Rev Cardiovasc Med2020       LitCov and CORD-19
8397First report of COVID-19-associated rhino-orbito-cerebral mucormycosis in pediatric patients with type 1 diabetes mellitus  

Coronavirus disease 2019 (COVID-19) is a major public health problem worldwide. These patients are at increased risk of developing secondary infections due to a combination of virus- and drug-induced immunosuppression. Recently, several countries have reported an emergence of COVID-19 associated mucormycosis (CAM), particularly among patients with uncontrolled diabetes, with India reporting an alarming increase in rhino-orbito-cerebral mucormycosis (ROCM) in post-COVID cases. Hyperglycemia and diabetic ketoacidosis (DKA) are the major underlying risk factors. So far, case reports and review articles have reported CAM only in adult patients. Here, we describe the first cases of COVID-19-associated ROCM in two pediatric patients with Type 1 diabetes mellitus (DM). Both the cases had asymptomatic infection with SARS-CoV-2 and developed ROCM during the course of treatment of DKA. None of them had exposure to systemic steroids. Imaging findings in both cases revealed involvement of orbit, paranasal sinuses, and brain with cavernous sinus thrombosis. The patients underwent craniotomy with evacuation of abscess. Microbiological and histopathological findings were consistent with the diagnosis of mycormycosis, with fungal culture growing Rhizopus arrhizus. Post-operatively, the patients received liposomal amphotericin B (LAMB) and systemic antibiotics. Retrobulbar injection of LAMB was given in an attempt to halt orbital disease progression. However, it wasn't successful and both of them had to undergo orbital exenteration eventually. ROCM is a rapidly progressive disease and prompt diagnosis with aggressive surgery and timely initiation of antifungal therapy can be life-saving. Physicians should have a high index of suspicion, so as to avoid a delayed diagnosis, particularly in post-COVID patients with uncontrolled diabetes.

J Mycol Med2021       LitCov and CORD-19
8398SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation  

The deployment of effective vaccines against SARS-CoV-2 is critical to eradicate the COVID-19 pandemic. Many licensed vaccines confer protection by inducing long-lived plasma cells (LLPC) and memory B cells (MBC), cell types canonically generated during germinal center (GC) reactions. Here, we directly compared two vaccine platforms −mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant− for their ability to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time. We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPC and MCB. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells. Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses.

Immunity2020       LitCov and CORD-19
8399COVID-19 Vaccination Coverage Among Insured Persons Aged ≥16 Years, by Race/Ethnicity and Other Selected Characteristics-Eight Integrated Healthcare Organizations, United States, December 14, 2020-May 15, 2021  

COVID-19 vaccination is critical to ending the COVID-19 pandemic. Members of minority racial and ethnic groups have experienced disproportionate COVID-19-associated morbidity and mortality (1); however, COVID-19 vaccination coverage is lower in these groups (2). CDC used data from CDC's Vaccine Safety Datalink (VSD)* to assess disparities in vaccination coverage among persons aged ≥16 years by race and ethnicity during December 14, 2020-May 15, 2021. Measures of coverage included receipt of ≥1 COVID-19 vaccine dose (i.e., receipt of the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of the Janssen COVID-19 vaccine [Johnson & Johnson]) and full vaccination (receipt of 2 doses of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of Janssen COVID-19 vaccine). Among 9.6 million persons aged ≥16 years enrolled in VSD during December 14, 2020-May 15, 2021, ≥1-dose coverage was 48.3%, and 38.3% were fully vaccinated. As of May 15, 2021, coverage with ≥1 dose was lower among non-Hispanic Black (Black) and Hispanic persons (40.7% and 41.1%, respectively) than it was among non-Hispanic White (White) persons (54.6%). Coverage was highest among non-Hispanic Asian (Asian) persons (57.4%). Coverage with ≥1 dose was higher among persons with certain medical conditions that place them at higher risk for severe COVID-19 (high-risk conditions) (63.8%) than it was among persons without such conditions (41.5%) and was higher among persons who had not had COVID-19 (48.8%) than it was among those who had (42.4%). Persons aged 18-24 years had the lowest ≥1-dose coverage (28.7%) among all age groups. Continued monitoring of vaccination coverage and efforts to improve equity in coverage are critical, especially among populations disproportionately affected by COVID-19.

MMWR Morb Mortal Wkly Rep2021       LitCov and CORD-19
8400Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial  

BACKGROUND: The oral, selective Janus kinase 1/2 inhibitor baricitinib has shown efficacy in studies of hospitalised adults with COVID-19. COV-BARRIER (NCT04421027) was a multinational, phase 3, randomised, double-blind, placebo-controlled trial of baricitinib in patients with confirmed SARS-CoV-2 infection. We aimed to evaluate the efficacy and safety of baricitinib plus standard of care in critically ill hospitalised adults with COVID-19 requiring invasive mechanical ventilation or extracorporeal membrane oxygenation. METHODS: This exploratory trial followed the study design of COV-BARRIER in a critically ill cohort not included in the main phase 3 trial. The study was conducted across 18 hospitals in Argentina, Brazil, Mexico, and the USA. Participants (aged ≥18 years) hospitalised with laboratory-confirmed SARS-CoV-2 infection on baseline invasive mechanical ventilation or extracorporeal membrane oxygenation were randomly assigned (1:1) to baricitinib (4 mg) or placebo once daily for up to 14 days in combination with standard of care. Participants, study staff, and investigators were masked to study group assignment. Prespecified endpoints included all-cause mortality through days 28 and 60, number of ventilator-free days, duration of hospitalisation, and time to recovery through day 28. The efficacy analysis was done in the intention-to-treat population and the safety analysis was done in the safety population. This trial is registered with ClinicalTrials.gov, NCT04421027. FINDINGS: Between Dec 23, 2020, and April 10, 2021, 101 participants were enrolled into the exploratory trial and assigned to baricitinib (n=51) or placebo (n=50) plus standard of care. Standard of care included baseline systemic corticosteroid use in 87 (86%) participants. Treatment with baricitinib significantly reduced 28-day all-cause mortality compared with placebo (20 [39%] of 51 participants died in the baricitinib group vs 29 [58%] of 50 in the placebo group; hazard ratio [HR] 0·54 [95% CI 0·31–0·96]; p=0·030; 46% relative reduction; absolute risk reduction 19%). A significant reduction in 60-day mortality was also observed in the baricitinib group compared with the placebo group (23 [45%] events vs 31 [62%]; HR 0·56 [95% CI 0·33–0·97]; p=0·027; 44% relative reduction; absolute risk reduction 17%). In every six baricitinib-treated participants, one additional death was prevented compared with placebo at days 28 and 60. The number of ventilator-free days did not differ significantly between treatment groups (mean 8·1 days [SD 10·2] in the baricitinib group vs 5·5 days [8·4] in the placebo group; p=0·21). The mean duration of hospitalisation in baricitinib-treated participants was not significantly shorter than in placebo-treated participants (23·7 days [SD 7·1] vs 26·1 days [3·9]; p=0·050). The rates of infections, blood clots, and adverse cardiovascular events were similar between treatment groups. INTERPRETATION: In critically ill hospitalised patients with COVID-19 who were receiving invasive mechanical ventilation or extracorporeal membrane oxygenation, treatment with baricitinib compared with placebo (in combination with standard of care, including corticosteroids) reduced mortality, which is consistent with the mortality reduction observed in less severely ill patients in the hospitalised primary COV-BARRIER study population. However, this was an exploratory trial with a relatively small sample size; therefore, further phase 3 trials are needed to confirm these findings. FUNDING: Eli Lilly and Company.

Lancet Respir Med2022       LitCov and CORD-19

(1) COVID-19 Open Research Dataset (CORD-19). 2020. Version 2022-06-02. Retrieved from https://ai2-semanticscholar-cord-19.s3-us-west-2.amazonaws.com/historical_releases.html. Accessed 2022-06-05. doi:10.5281/zenodo.3715506
(2) Chen Q, Allot A, & Lu Z. (2020) Keep up with the latest coronavirus research, Nature 579:193 and Chen Q, Allot A, Lu Z. LitCovid: an open database of COVID-19 literature. Nucleic Acids Research. 2020. (version 2023-01-10)
(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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